Human Epilepsy Project 3 (HEP3)

Human Epilepsy Project 3: Newly Diagnosed Idiopathic Generalized Epilepsy

By carrying a careful, large-scale and ambitious prospective study of a cohort of participants with generalized epilepsy, the study team hopes to clarify the likelihood of response and remission in this type of epilepsy, and try to explore the underlying biological drivers of treatment response, including novel realms of exploration such as impact of the microbiome, and genetics. The identification of biomarkers that predict the likelihood of disease response would allow epilepsy patients to make more informed decisions about the factors affecting their quality of life, including plans for driving, relationships, pregnancy, schooling, work, and play. In addition to its impact on clinical care, the data and specimens collected in HEP3, including sequential electrophysiology, biochemical profiles and neuroimaging and banked DNA for future genomics studies, have the potential to provide new insights into the biological basis of IGE, thereby advancing the discovery of effective treatments and cures. By enrolling both newly diagnosed subjects (prognosis unknown) as well as subjects with established IGE who are already determined to be treatment resistant or treatment responsive, the study team can immediately test potential biomarkers in a confirmation cohort, which will accelerate identification of predictive biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Generalized Epilepsy

• Study Type: Observational
• Enrollment (Estimated): 380

Contacts and Locations

• Study Contact: Name: Jacqueline French, MD; Phone Number: 646-558-0839; Email: Jacqueline.French@nyulangone.org
• Study Contact Backup: Name: Orrin Devinsky, MD; Phone Number: 646-558-0803; Email: Orrin.Devinsky@nyulangone.org

Study Locations

• Australia
  • Clayton VIC
    • Melbourne, Clayton VIC, Australia, 3800
      • Recruiting
      • Monash University
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco (UCSF)
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Recruiting
      • Georgetown University
  • Florida
    • Miami, Florida, United States, 33146
      • Recruiting
      • University of Miami
  • Maine
    • Portland, Maine, United States, 04102
      • Recruiting
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Not yet recruiting
      • The Johns Hopkins Hospital
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Mid-Atlantic Epilepsy Sleep Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
    • Saint Paul, Minnesota, United States, 55113
      • Recruiting
      • Minnesota Epilepsy Group
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Recruiting
      • St. Barnabas Medical Center
  • New York
    • New York, New York, United States, 10029
      • Not yet recruiting
      • Mount Sinai Hospital
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health - Comprehensive Epilepsy Center (CEC)
      • Principal Investigator: Orrin Devinsky, MD
      • Sub-Investigator: Jacqueline French, MD
    • New York, New York, United States, 10065
      • Recruiting
      • Northwell Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
  • Texas
    • San Antonio, Texas, United States, 77030
      • Recruiting
      • University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Not yet recruiting
      • University of Utah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with newly diagnosed IGE, as well as a cohort of subjects with established IGE.

Description

Cohort 1: Newly Diagnosed IGE

Inclusion criteria:

1. Age ≥13 years at time of enrollment
2. Age ≥8 years at time of seizure onset
3. Clinical seizure(s) and history consistent with IGE. The only permitted seizure types are absence, myoclonus or generalized tonic-clonic convulsions
4. Occurrence of at least 1 seizure of any type in the 6 months prior to treatment

5. Patients must have one of the following:

   • GTCSs alone accompanied by generalized spike-wave consistent with IGE per adjudication review
   • GTCSs with a history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
   • GTCSs associated with a history of absence and/or myoclonus, not accompanied by generalized spike-wave consistent with IGE per adjudication review
   • A clear history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
6. Availability of a complete medication history since initiation of treatment, including doses and date of initiation
7. No competing cause of epilepsy (e.g. traumatic brain injury)
8. AED treatment (for seizures) instituted not more than 12 months before enrollment

Exclusion Criteria

1. Focal epilepsy
2. Generalized/focal epilepsy mixed syndromes
3. Progressive neurological disorder (brain tumor, Alzheimer's disease, progressive myoclonic epilepsy, etc.)
4. Epileptic or developmental encephalopathy
5. Major medical co-morbidities (e.g. renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease)
6. Autism Spectrum Disorder
7. History of chronic drug or alcohol abuse (misuse or excessive use that interferes with activities of daily living) within the last 2 years
8. Seizures only during pregnancy
9. History of previous or current significant psychiatric disorder that would interfere with study requirements

Cohort 2: Longstanding Treatment Responsive

Inclusion Criteria:

1. Age ≥13 years at time of enrollment
2. Age ≥8 years at time of seizure onset
3. Clinical seizure(s) and history consistent with IGE. The only permitted seizure types are absence, myoclonus or generalized tonic-clonic convulsions

4. Patients must have had one of the following:

   1. GTCSs alone accompanied by generalized spike-wave consistent with IGE per adjudication review
   2. GTCSs with a history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
   3. GTCSs associated with a history of absence and/or myoclonus, not accompanied by generalized spike-wave consistent with IGE per adjudication review
   4. A clear history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
5. Availability of a complete medication history since initiation of treatment, including doses and date of initiation
6. No competing cause of epilepsy (e.g. traumatic brain injury)

7. Two years of well-controlled seizures.

   1. No convulsive seizures in the last two years
   2. Myoclonic or absence seizures must be rare (<2 per year) and non-disabling
   3. Ongoing therapy with > 1 antiseizure medication

Exclusion Criteria:

1. Focal epilepsy
2. Paroxysmal nonepileptic seizures
3. Generalized/focal epilepsy mixed syndromes
4. Progressive neurological disorder (brain tumor, Alzheimer's disease, progressive myoclonic epilepsy, etc.)
5. Epileptic or developmental encephalopathy
6. Major medical co-morbidities (e.g. renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease)
7. Autism Spectrum Disorder
8. History of chronic drug or alcohol abuse (misuse or excessive use that interferes with activities of daily living) within the last 2 years
9. Seizures only during pregnancy
10. History of previous or current significant psychiatric disorder that would interfere with study requirements

Cohort 3: Longstanding IGE, Treatment Resistant

Inclusion Criteria:

1. Age ≥13 years at time of enrollment
2. Age ≥8 years at time of seizure onset
3. Clinical seizure(s) and history consistent with IGE. The only permitted seizure types are absence, myoclonus or generalized tonic-clonic convulsions
4. Occurrence of at least 1 seizure of any type in the 6 months prior to treatment onset

5. Patients must have had one of the following:

   1. GTCSs alone accompanied by generalized spike-wave consistent with IGE per adjudication review
   2. GTCSs with a history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
   3. GTCSs associated with a history of absence and/or myoclonus, not accompanied by generalized spike-wave consistent with IGE per adjudication review
   4. A clear history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
6. Availability of a complete medication history since initiation of treatment. This should include doses and date of initiation if possible, but minimum information would include name of drug, approximate duration of administration and reason for discontinuation, if applicable.
7. No competing cause of epilepsy (e.g. traumatic brain injury)

8. Treatment resistant IGE

   1. Initiation of treatment at least 2 years prior to enrollment
   2. Treatment resistance, as defined by failure of adequate trials of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination to achieve seizure freedom). ASMs taken at enrollment would count towards this minimum.
   3. Either or both of the following two:

   i. One GTCC per year over the last 2 years. ii. Any type of seizure at least every 3 months which can consist of either: disabling myoclonus or absence (in the opinion of the subject and investigator) or GTCC d. Such seizures were not primarily due to significant illness (e.g, URI is not significant unless temperature >101oF (38.3oC), nonadherence to antiseizure medications or >2 alcoholic beverages within 48 hrs of seizure e. Ongoing therapy with > 1 antiseizure medication

Exclusion Criteria:

1. Focal epilepsy
2. Paroxysmal nonepileptic seizures
3. Generalized/focal epilepsy mixed syndromes
4. Progressive neurological disorder (brain tumor, Alzheimer's disease, progressive myoclonic epilepsy, etc.)
5. Epileptic or developmental encephalopathy
6. Major medical co-morbidities (e.g. renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease)
7. Autism Spectrum Disorder
8. History of chronic drug or alcohol abuse (misuse or excessive use that interferes with activities of daily living) within the last 2 years
9. Seizures only during pregnancy
10. History of previous or current significant psychiatric disorder that would interfere with study requirements
11. History of/suspicion of provoked seizures accounting for 25% or more of seizures over the prior 2 years (eg alcohol, non-adherence, significant sleep deprivation).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cohort 1: Newly Diagnosed Idiopathic Generalized Epilepsy (IGE); Cohort 1 will have IGE that was diagnosed within the prior year. We will follow these participants for a minimum of two years.
Cohort 2: Longstanding Treatment Responsive; Cohort 2 will consist of subjects with established IGE who have been responsive to treatment.
Cohort 3: Longstanding IGE, Treatment Resistant; Cohort 3 will consist of patients with established treatment-resistant IGE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Individual Seizures	Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)	Baseline
Number of Cluster Seizures	Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)	Baseline
Number of episodes of non-adherence	Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)	Baseline
Average daily steps	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study.	Baseline
Average distance walked	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study.	Baseline
Average heart rate	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study.	Baseline
Average daily sleep duration	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study. Using the Embleema Patient Web App, participants will be able to consult their activity and sleep data in interactive graphs.	Baseline
Average daily wake duration	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study. Using the Embleema Patient Web App, participants will be able to consult their activity and sleep data in interactive graphs.	Baseline
Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score	QOLIE-10 assesses the patient's quality of life. There are 11 total items. The total score range is 10-51; with higher scores indicating greater impairment. The total score is the sum of scores for all questions divided by the number of items answered. Thus, if a patient skipped an item, it is not reflected in the total score.	Baseline, Month 12
Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score	QOLIE-10 assesses the patient's quality of life. There are 11 total items. The total score range is 10-51; with higher scores indicating greater impairment. The total score is the sum of scores for all questions divided by the number of items answered. Thus, if a patient skipped an item, it is not reflected in the total score.	Baseline, Month 24
Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score	QOLIE-10 assesses the patient's quality of life. There are 11 total items. The total score range is 10-51; with higher scores indicating greater impairment. The total score is the sum of scores for all questions divided by the number of items answered. Thus, if a patient skipped an item, it is not reflected in the total score.	Month 12, Month 24
Change in General Anxiety Disorder-7 Screener (GAD-7) Score	This will only be reported for adults. GAD-7 consists of 7 problems. Participants report how often they have been bothered by the 7 problems over the last 2 weeks on a Likert Scale from 0 (not at all) to 3 (nearly every day). The total score range is 0-21; the higher the score, the more severe the anxiety. 0-4=minimal anxiety, 5-9=mild, 10-14=moderate, 15-21=severe anxiety.	Baseline, Month 12
Change in General Anxiety Disorder-7 Screener (GAD-7) Score	This will only be reported for adults. GAD-7 consists of 7 problems. Participants report how often they have been bothered by the 7 problems over the last 2 weeks on a Likert Scale from 0 (not at all) to 3 (nearly every day). The total score range is 0-21; the higher the score, the more severe the anxiety. 0-4=minimal anxiety, 5-9=mild, 10-14=moderate, 15-21=severe anxiety.	Baseline, Month 24
Change in General Anxiety Disorder-7 Screener (GAD-7) Score	This will only be reported for adults. GAD-7 consists of 7 problems. Participants report how often they have been bothered by the 7 problems over the last 2 weeks on a Likert Scale from 0 (not at all) to 3 (nearly every day). The total score range is 0-21; the higher the score, the more severe the anxiety. 0-4=minimal anxiety, 5-9=mild, 10-14=moderate, 15-21=severe anxiety.	Month 12, Month 24
Columbia Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) - 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention	Baseline
Columbia Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) - 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention	Month 12
Columbia Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) - 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention	Month 24
Cogstate Neuropsychological Assessment Score	The Cogstate is a battery of online computerized tests that assesses functions such as attention, memory, and processing speed. Scores are normalized to the range of 0-100th percentile based on speed of test completion and task accuracy. A higher percentile score indicates higher levels of cognitive functioning within the tested domain as compared to controls.	Baseline
Cogstate Neuropsychological Assessment Score	The Cogstate is a battery of online computerized tests that assesses functions such as attention, memory, and processing speed. Scores are normalized to the range of 0-100th percentile based on speed of test completion and task accuracy. A higher percentile score indicates higher levels of cognitive functioning within the tested domain as compared to controls.	Month 12
Cogstate Neuropsychological Assessment Score	The Cogstate is a battery of online computerized tests that assesses functions such as attention, memory, and processing speed. Scores are normalized to the range of 0-100th percentile based on speed of test completion and task accuracy. A higher percentile score indicates higher levels of cognitive functioning within the tested domain as compared to controls.	Month 24
Wide Range Achievement Test (WRAT-4) Score	WRAT4 is an academic skills assessment which measures reading skills, math skills, spelling, and comprehension. Only the Word Reading portion of the assessment will be administered. The total raw score range is from 0-70, with a normalized score range of 55-145. The higher the score, the more advanced the participant's reading comprehension skills for their age range.	Baseline

Collaborators and Investigators

• Sponsor: NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsy, Generalized
• Other Study ID Numbers: 19-01030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal will have access to the data upon reasonable request. All requests for study data will be submitted using a standardized form that will be available on the HEP3 website (www.humanepilepsyproject.org).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No